Úvod: Cílem této studie bylo porovnat hodnoty interleukinu-6 v pupečníkové a periferní krvi novorozence. Klinickým cílem bylo zjistit, zda lze vyšetřením krve z pupečníku nahradit brzký postnatální odběr periferní krve. Pacienti a metody: Do studie byli zahrnuti novorozenci (< 35. týden gestace) narození v roce 2016–2018 ve Fakultní nemocnici Olomouc. U těchto novorozenců se zároveň podařilo odebrat dostatečné množství krve z pupečníku. Výsledky: Párový odběr se zdařil u 73 novorozenců. Mezi pupečníkovou a periferní hodnotou interleukinu-6 byl zjištěn významný rozdíl (p < 0,001). Medián prvního měření (pupečníková krev) byl 6,5 ng/l, medián druhého měření (periferní krev) 56 ng/l. Nárůst je téměř desetinásobný. Závěr: Hodnoty interleukinu-6 z pupečníkové krve a z časného postnatálního odběru se podstatně liší. Na tuto skutečnost je nutné myslet při jeho klinickém využití.
Introduction: The aim of this study was to compare interleukin-6 values in umbilical cord and peripheral blood of newborns. The clinical goal was to determine whether the examination of cord blood can replace early postnatal peripheral blood collection. Patients and methods: Study included premature newborns (< 35th week of gestation) born in 2016-2018 at Olomouc University Hospital. At the same time, it was possible to collect a sufficient amount of blood from the umbilical cord in these newborns. Results: Paired sampling was successful in 73 of these newborns. A significant difference (p < 0,001) was found between the umbilical cord and peripheral interleukin-6 values. The median of the first measurement (cord blood) was 6,5 ng/l, the median of the second measurement (peripheral blood) was 56 ng/l. The increase is almost ten times bigger. Conclusion: The difference of values between interleukin-6 from umbilical cord blood and from early postnatal collection are significantly different and it is necessary to keep it in mind during its clinical use.
- MeSH
- fetální krev imunologie MeSH
- interleukin-6 * analýza izolace a purifikace krev MeSH
- krev imunologie MeSH
- lidé MeSH
- novorozenec nedonošený imunologie krev MeSH
- novorozenec MeSH
- novorozenecká sepse diagnóza etiologie imunologie prevence a kontrola MeSH
- prospektivní studie MeSH
- pupečník imunologie krevní zásobení MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- alergie * imunologie MeSH
- dítě MeSH
- fetální krev imunologie MeSH
- hematologické testy MeSH
- probiotika MeSH
- sexuální faktory * MeSH
- výzkum MeSH
- Check Tag
- dítě MeSH
- mužské pohlaví MeSH
- Publikační typ
- rozhovory MeSH
BACKGROUND: The benefit of probiotics in newborn children in relation to allergy and general morbidity later in life appears to be controversial. Allergic diseases represent an increasingly important health problem worldwide in recent years. This is evident in all age groups. The occurrence of allergic illnesses also continues to rise exponentially, and thus the use of preventive and prognostic methods, particularly in children with an inherently higher risk of allergy, is gaining increased importance. Since the advent of probiotics the effect of probiosis on immunity through alterations of composition and function of the human gut microbiome has been increasingly studied. The exact mechanisms have not yet been clearly defined. The Academy of Sciences of the Czech Republic (The Czech Academy of Sciences has suggested that the expression of TH1 and TH2 cytokines in umbilical blood is associated with an increased risk of allergies. The counter -balance of Th1 and Th2 affect Immunoglobulin E (IgE) production and maturation of the gastrointestinal tract epithelium. CASE PRESENTATION: We examined IgE levels in 3000 samples of umbilical blood taken from children born into families with a positive history of allergy in one or both parents from 2007 to 2017. At the age of ten days, those with high IgE were given Colinfant Newborn (a lyophilized non-pathogenic strain of Escherichia.coli) for one month, three times weekly. At 15 months and three years we investigated the levels of Immunoglobulins E,A and G, and the incidence of illness and allergy. The results revealed that allergy and high umbilical IgE is strongly linked with family history (p ≤ 0.001). We also detected differences in seasonality, especially with regards to pollen allergies. Eighty percent of children treated with Colinfant Newborn had significantly reduced IgE and morbidity at 13-15 months and 3 years, and furthermore without any clinical signs of allergy. Normalization of Immunoglobulins A and G was seen in 90% of treated subjects (p ≤ 0.001). These levels significantly correlated with an almost negligible morbidity up to 4 years of life. Colinfant Newborn, a lyophilized strain of Esherichia coli (E. coli), and a normal component of intestinal flora, readily colonizes the intestinal tract. It's long term presence significantly stimulates the production of specific and non-specific intestinal antibodies. and optimalizes immune development through tolerance. In our study Colinfant Newborn reduced the incidence of infections later in life by safely and effectively normalizing immunoglobulin levels in the majority of treated patients. CONCLUSION: Our study strongly suggests as positive effect of physiological Escherichia coli on the microbiome of newborn children as evidenced by a significantly reduced incidence of allergy and morbidity when applied early in life. These benefits appear to be strongly strain specific.
- MeSH
- alergie diagnóza farmakoterapie MeSH
- biologická terapie metody MeSH
- časové faktory MeSH
- centra terciární péče MeSH
- fetální krev imunologie MeSH
- hospitalizace statistika a číselné údaje MeSH
- imunoglobulin E krev MeSH
- kohortové studie MeSH
- lidé MeSH
- mikrobiota MeSH
- následné studie MeSH
- novorozenec MeSH
- novorozenecký screening metody MeSH
- retrospektivní studie MeSH
- senzitivita a specificita MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Allergic diseases represent a major issue in clinical and experimental immunology due to their high and increasing incidence worldwide. Allergy status of the mother remains the best predictor of an individual's increased risk of allergy development. Dysregulation of the balance between different branches of immune response, chiefly excessive polarization towards Th2, is the underlying cause of allergic diseases. Regulatory T cells (Tregs) play a pivotal role in the timely establishment of physiological immune polarization and are crucial for control of allergy. In our study we used flow cytometry to assess Tregs in cord blood of newborns of healthy (n = 121) and allergic (n = 108) mothers. We observed a higher percentage of Tregs (CD4+CD25+CD127lowFoxP3+) in cord blood of children of allergic mothers. However, the percentage of cells expressing extracellular (PD-1, CTLA-4, GITR) and intracellular (IL-10, TGF-β) markers of function was lower (significantly for PD-1 and IL-10) within Tregs of these children. Furthermore, Helios- induced Tregs in the cord blood of children of allergic mothers were decreased. These results were supported by a decrease in plasma levels of IL-10 and TGF-β in cord blood of newborns of allergic mothers, implying lower tolerogenic capacity on the systemic level. Taken together, these findings reflect deficient function of Tregs in the group with higher risk of allergy development. This may be caused by a lower maturation status of the immune system, specifically Tregs, at birth. Such immaturity may represent an important mechanism involved in the increased risk of allergy in children of allergic mothers.
- MeSH
- alergie krev imunologie MeSH
- cytokiny krev MeSH
- fetální krev imunologie MeSH
- imunoglobulin E krev MeSH
- lidé MeSH
- matky MeSH
- náchylnost k nemoci krev imunologie MeSH
- novorozenec MeSH
- regulační T-lymfocyty imunologie MeSH
- riziko MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The growing knowledge of the key role of microbiota in the maturation of neonatal immune system suggests that manipulation of microbiota could be exploited in hampering allergy development. In this study, Escherichia coli O83:K24:H31 (EcO83) was administered to newborns that were followed prospectively. Several immunological characteristics (cytokines, specific IgE, total T regulatory cells (Treg) and subpopulation of natural Treg (nTreg) and induced Treg (iTreg)) were tested in peripheral blood of 8-year-old children. Incidence of allergic disease was decreased in EcO83 supplemented children and significantly elevated levels of IL-10 and IFN-ɣ were detected in serum of EcO83 supplemented children. Probiotic supplementation did not influence the numbers of the total Treg population but their functional capacity (intracellular expression of IL-10) was significantly increased in children supplemented with EcO83 in comparison to non-supplemented children. Morover, decreased proportion of iTreg was present in peripheral blood of non-supplemented in comparison to EcO83 supplemented children. Finally, stimulation of cord blood cells with EcO83 promoted both gene expression and secretion of IL-10 and IFN-ɣ suggesting that beneficial effect of EcO83 in prevention of allergy development could be mediated by promotion of regulatory responses (by IL-10) and Th1 immune response (by IFN-ɣ).
- MeSH
- alergie epidemiologie imunologie MeSH
- dítě MeSH
- Escherichia coli fyziologie MeSH
- fetální krev cytologie imunologie mikrobiologie MeSH
- imunitní systém MeSH
- incidence MeSH
- interferon gama krev MeSH
- interleukin-10 krev MeSH
- kultivované buňky MeSH
- lidé MeSH
- mikrobiota imunologie MeSH
- novorozenec MeSH
- probiotika terapeutické užití MeSH
- prospektivní studie MeSH
- regulační T-lymfocyty imunologie MeSH
- Th1 buňky imunologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- COLIFANT NEWBORN,
- MeSH
- anamnéza MeSH
- časná přecitlivělost * farmakoterapie krev prevence a kontrola MeSH
- dítě MeSH
- Escherichia coli imunologie MeSH
- fetální krev imunologie MeSH
- imunoglobulin A analýza imunologie MeSH
- imunoglobulin E analýza MeSH
- kojenec MeSH
- lidé MeSH
- morbidita MeSH
- novorozenec MeSH
- odběr fetální krve MeSH
- střevní mikroflóra imunologie účinky léků MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
Beneficial effect of maternal milk is acknowledged, but there is still question whether maternal milk from allergic mother is as good as from healthy one. In our study, we have assayed the effect of cells from colostrum of healthy and allergic mothers on gene expression of cytokines in cord blood cells of newborns of healthy and allergic mothers. Cytokines typical for Th1 (IL-2, IFN-gamma), Th2 (IL-4, IL-13), Tregs (IL-10, TGF-beta), and IL-8 were followed. We were not able to detect significant influence of colostral cells on gene expression of cytokines in cord blood after 2-day coculture using Transwell system. There was no difference in gene expression of cytokines in nonstimulated cord blood cells of newborns of healthy and allergic mothers, but generally increased gene expression of cytokines except IL-10 and TGF-beta after polyclonal stimulation was detected in cord blood cells of children of allergic mothers. There was no difference in IL-10 expression in stimulated cord blood cells of children of healthy and allergic mothers. Gene expression of TGF-beta was even decreased in stimulated cord blood cells of children of allergic mothers in comparison to healthy ones. We have not observed difference in the capacity of colostral cells of healthy and allergic mothers to influence gene expression of cytokines in cord blood cells, but we have described difference in the reactivity of cord blood cells between children of allergic and healthy mothers.
- MeSH
- alergie krev genetika imunologie MeSH
- cytokiny krev MeSH
- dospělí MeSH
- exprese genu MeSH
- fetální krev chemie imunologie MeSH
- interleukin-10 genetika imunologie MeSH
- interleukin-13 krev MeSH
- interleukin-4 krev MeSH
- kojenec MeSH
- kolostrum chemie imunologie MeSH
- lidé MeSH
- mladý dospělý MeSH
- novorozenec MeSH
- těhotenství MeSH
- Th1 buňky imunologie MeSH
- Th2 buňky imunologie MeSH
- Check Tag
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The diversity, architecture, and dynamics of the TCR repertoire largely determine our ability to effectively withstand infections and malignancies with minimal mistargeting of immune responses. In this study, we have employed deep TCRβ repertoire sequencing with normalization based on unique molecular identifiers to explore the long-term dynamics of T cell immunity. We demonstrate remarkable stability of repertoire, where approximately half of all T cells in peripheral blood are represented by clones that persist and generally preserve their frequencies for 3 y. We further characterize the extremes of lifelong TCR repertoire evolution, analyzing samples ranging from umbilical cord blood to centenarian peripheral blood. We show that the fetal TCR repertoire, albeit structurally maintained within regulated borders due to the lower numbers of randomly added nucleotides, is not limited with respect to observed functional diversity. We reveal decreased efficiency of nonsense-mediated mRNA decay in umbilical cord blood, which may reflect specific regulatory mechanisms in development. Furthermore, we demonstrate that human TCR repertoires are functionally more similar at birth but diverge during life, and we track the lifelong behavior of CMV- and EBV-specific T cell clonotypes. Finally, we reveal gender differences in dynamics of TCR diversity constriction, which come to naught in the oldest age. Based on our data, we propose a more general explanation for the previous observations on the relationships between longevity and immunity.
- MeSH
- buněčné klony MeSH
- časové faktory MeSH
- dítě MeSH
- dlouhověkost MeSH
- dospělí MeSH
- fetální krev cytologie imunologie MeSH
- imunodominantní epitopy MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- receptory antigenů T-buněk alfa-beta genetika imunologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- simulace molekulární dynamiky MeSH
- software MeSH
- stárnutí * MeSH
- T-lymfocyty imunologie fyziologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Erytrocytární aloimunizace (izoimunizace, hemolytické onemocnění plodu a novorozence – HON) se v současnosti díky rutinní imunoprofylaxi anti-D imunoglobulinem vyskytuje sporadicky. Výskyt atypických aloimunizací non-RhD-antigeny zůstává neměnný, poněvadž není známa profylaxe a ani prevence nezajišťuje stoprocentní účinnost. Pokud se imunoprofylaxe anti-D imunoglobulinem neprovede nebo selže, hrozí vznik hemolytického onemocnění plodu a novorozence. Každý případ je potom unikátní (specifita a typ protilátky, blokující protilátky v séru matky, antigenní výbava erytrocytů plodu, gestační stáří při začátku onemocnění atd). Pokroky v genové diagnostice, imunohematologii a dopplerovské ultrasonografii významně snižují frekvenci nutných invazivních zákroků v diagnostice a léčbě senzibilizovaného těhotenství. Intraumbilikální přísně intravenózní transfuze pod ultrasonografickou kontrolou je první metodou volby léčby případů s těžkou anémií plodu i při rozvinutém hydropsu. Konzultace a léčba se soustřeďují do center s perfektní porodnickou a neonatologickou péčí a nepřetržitou operační pohotovostí. Klíčová slova: anti-D-imunoglobulin – erytrocytární aloimunizace – hemolytické onemocnění plodu a novorozence – imunoprofylaxe anti-D-imunoglobulinem – intraumbilikální intravenózní transfuze
The erythrocyte alloimmunization (isoimmunization, hemolytic disease of the fetus and newborn – HON) occurs sporadically at present, thanks to routine immunoprophylaxis with anti-D immunoglobulin. The occurrence of atypical alloimmunizations related to non-RhD-antigens remains unchanged, as there is no prophylaxis known and even the prevention does not provide one hundred percent efficiency. When anti-D immunoglobulin immunoprophylaxis is not undertaken or fails, the threat of hemolytic disease of the fetus and newborn arises. Every case is then unique (specificity and type of antibody, blocking antibodies in maternal serum, antigenic make-up of fetal erythrocytes, gestational age at the disease onset etc). The advancements in genetic diagnostics, immunohematology and Doppler ultrasonography significantly reduce the frequency of necessary invasive interventions in the diagnostics and treatment of sensibilized pregnancy. Intraumbilical strictly intravenous transfusion under ultrasound guidance is the first-line method of therapy for cases of severe fetal anemia as well as advanced hydrops. Consultations and treatment are provided in the centres for comprehensive obstetrical and neonatal care with continuous intervention preparedness. Key words: anti-D immunoglobulin – erythrocyte alloimmunization – hemolytic disease of the fetus and newborn – anti-D immunoglobulin immunoprophylaxis – intraumbilical intravenous transfusion
- Klíčová slova
- intraumbilikální intravenózní transfuze,
- MeSH
- anemie diagnóza MeSH
- arteria cerebri media MeSH
- Coombsův test MeSH
- fetální krev imunologie MeSH
- hematologické komplikace těhotenství * MeSH
- hemolytická nemoc plodu a novorozence * diagnóza prevence a kontrola terapie MeSH
- imunizace metody MeSH
- imunologické faktory aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- intrauterinní krevní transfuze * kontraindikace metody škodlivé účinky MeSH
- lidé MeSH
- nemoci plodu diagnóza MeSH
- novorozenec MeSH
- plod krevní zásobení MeSH
- postnatální péče MeSH
- předčasný porod MeSH
- pupečník imunologie krevní zásobení MeSH
- Rh izoimunizace * diagnóza prevence a kontrola terapie MeSH
- Rho(D) imunoglobulin * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- rychlost toku krve MeSH
- těhotenství MeSH
- transfuze erytrocytů MeSH
- ultrasonografie dopplerovská MeSH
- ultrasonografie prenatální MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- alergie * diagnóza prevence a kontrola MeSH
- aplikace orální MeSH
- dítě MeSH
- fetální krev imunologie MeSH
- hodnocení léčiv MeSH
- imunoglobulin A analýza MeSH
- imunoglobulin E analýza MeSH
- interleukin-4 imunologie MeSH
- interpretace statistických dat MeSH
- kojenec MeSH
- lidé MeSH
- longitudinální studie MeSH
- novorozenec MeSH
- odběr fetální krve MeSH
- předškolní dítě MeSH
- probiotika MeSH
- raná péče MeSH
- studie případů a kontrol MeSH
- T-lymfocyty pomocné-indukující imunologie MeSH
- vakcíny proti Escherichia coli * aplikace a dávkování farmakokinetika terapeutické užití MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- předškolní dítě MeSH